尾加压素Ⅱ mRNA在正常肾上腺髓质和嗜铬细胞瘤组织中的表达

目的　研究尾加压素Ⅱ (UrotensinⅡ ,UⅡ )mRNA在正常肾上腺髓质和嗜铬细胞瘤组织中的表达。方法　正常肾上腺髓质组织取自 9例意外死亡的中青年 ,嗜铬细胞瘤组织取自 19例患者手术切除标本 ,分别提取组织总RNA ,用逆转录 聚合酶链反应方法进行研究 ,以UⅡ和内参照GAPDH(甘油醛 3 三磷酸脱氢酶 )进行同管扩增 ,以扩增的目的条带灰度和内参照条带灰度比值UⅡ /GAPDH进行UⅡmRNA表达的半定量分析。结果　UⅡ的PCR扩增产物长度为 385bp ,测序结果与GeneBank所登记碱基序列相同率为 99.7%。正常肾上腺髓质和嗜铬细胞瘤组织UⅡ /GAPDH比值分别为 0 .6 9± 0 .2 9和 0 .2 2± 0 .18(P <0 .0 5 )。结论　UⅡmRNA在正常肾上腺髓质和嗜铬细胞瘤组织中均有表达 ,嗜铬细胞瘤组织中的表达低于正常肾上腺髓质组织。     

Relationship of the plasma urotensin Ⅱ with proadrenomedullin N-terminal 20 peptide in patients with congestive heart failure

Objective: To understand the role of urotensin Ⅱ ( U Ⅱ ) and proadrenomedullin N-terminal 20 peptide ( PAMP) , a fragment of proadrenomedullin ( proADM ) possessing biological activity, in the pathophysiological process of congestive heart failure (CHF) by observing the variation of their plasma levels and exploring their interrelations. Methods: Plasma U Ⅱ and PAMP levels were measured by radioimmunoassay in 52 patients with CHF and 14 healthy subjects. Left ventricular ejection fraction (LVEF) and the ratio of E/A were determined by echocardiography. Results: The plasma U Ⅱ level was significantly lower in patients with CHF than the healthy subjects (1.5±1.0 pg/ml vs 4. 3±1.2 pg/ml, P < 0.05), while plasma PAMP level was significantly higher in the former group (30. 6±5. 8 pg/ml vs 21.0±6.6 pg/ml P < 0. 05 ). The levels of U Ⅱ and PAMP were parallel with the severity of CHF, and significant correlation of plasma levels of U Ⅱ with LVEF (r=0.530, P=0.000) and the ratio of E/A (r=0.618, P = 0.     

Contraction of isolated guinea-pig ileum by urotensin II via activation of ganglionic cholinergic neurons and acetylcholine release

Urotensin II and its receptor are expressed in the gastrointestinal tract of mice, but the effects of urotensin II on the gastrointestinal functions have not been established. In the present study, we investigated the effects of human urotensin II on a segment of the guinea-pig ileum. The addition of urotensin II induced contraction of the ileum in concentration-manner (-log EC(50) value was 8.13+/-0.21). The response by urotensin II was extracellular CaCl(2)-dependent and easily desensitized. Like nicotine, the contraction induced by 100 nM urotensin II was inhibited by treatment with atropine, hexamethonium, D-tubocurarine, tetrodotoxin or hemicholinium-3, and enhanced by physostigmine. Treatment with omega-conotoxin GVIA (an inhibitor of N-type Ca(2+) channels, 300 nM) inhibited 100 nM urotensin II- and 4 microM nicotine-, but not 3 microM acetylcholine-, induced contraction. Both urotensin II and nicotine stimulated [(3)H]choline release in a tetrodotoxin-sensitive manner from the prelabeled slices of the ileum. These findings suggest that urotensin II stimulated acetylcholine release from the ganglionic cholinergic neurons and thus stimulated contraction via muscarinic acetylcholine receptors in the guinea-pig ileum. Urotensin II receptor system in the myenteric neurons may regulate the gastrointestinal functions.     

Urotensin Ⅱ-induced insulin resistance is mediated by NADPH oxidase-derived reactive oxygen species in Hep G2 cells

AIM: To investigated the effects of urotensin Ⅱ(UII) on hepatic insulin resistance in Hep G2 cells and the potential mechanisms involved.METHODS: Human hepatoma Hep G2 cells were cultured with or without exogenous UII for 24 h, in the presence or absence of 100 nmol/L insulin for the last 30 min. Glucose levels were detected by the glucoseoxidase method and glycogen synthesis was analyzed by glycogen colorimetric/fluorometric assay. Reactive oxygen species(ROS) levels were detected with a multimode reader using a 2′,7′-dichlorofluorescein diacetate probe. The protein expression and phosphorylation levels of c-Jun N-terminal kinase(JNK), insulin signal essential molecules such as insulin receptor substrate-1(IRS-1), protein kinase B(Akt), glycogen synthase kinase-3β(GSK-3β), and glucose transporter-2(Glut 2), and NADPH oxidase subunits such as gp91 phox, p67 phox, p47 phox, p40 phox, and p22 phox were evaluated by Western blot.RESULTS: Exposure to 100 nmol/L UII reduced the insulin-induced glucose consumption(P 0.05)and glycogen content(P 0.01) in Hep G2 cells compared with cells without UII. UII also abolished insulin-stimulated protein expression(P 0.01) and phosphorylation of IRS-1(P 0.05), associated with down-regulation of Akt(P 0.05) and GSK-3β(P 0.05) phosphorylation levels, and the expression of Glut 2(P 0.001), indicating an insulin-resistance state in Hep G2 cells. Furthermore, UII enhanced the phosphorylation of JNK(P 0.05), while the activity of JNK, insulin signaling, such as total protein of IRS-1(P 0.001), phosphorylation of IRS-1(P 0.001) and GSK-3β(P 0.05), and glycogen synthesis(P 0.001) could be reversed by pretreatment with the JNK inhibitor SP600125. Besides, UII markedly improved ROS generation(P 0.05) and NADPH oxidase subunit expression(P 0.05). However, the antioxidant/NADPH oxidase inhibitor apocynin could decrease UII-induced ROS production(P 0.05), JNK phosphorylation(P 0.05), and insulin resistance(P 0.05) in HepG 2 cells. CONCLUSION: UII induces insulin resistance, and this can be reversed by JNK inhibitor SP600125 and antioxidant/NADPH oxidase inhibitor apocynin targeting the insulin signaling pathway in HepG 2 cells.     

体位性心动过速综合征儿童血浆尾加压素Ⅱ和儿茶酚胺抑素的变化及意义

目的：通过检测体位性心动过速综合征（postural orthostatic tachycardia syndrome, POTS）患儿心血管活性肽含量的变化,探索其发病机制。方法：采用临床对照研究的方法,POTS组为于北京大学第一医院儿科门诊就诊的POTS儿童46例（平均12.1±2.8岁）,对照组为健康儿童20例（平均11.5±3.6岁）,采用酶免疫法测定血浆尾加压素Ⅱ（urotensin Ⅱ, UII）及儿茶酚胺抑素（catestatin,Cs）浓度,分析POTS组患儿血管活性肽含量的变化及与直立后心率变化的相关性。结果：与对照组相比,POTS组患儿血浆UII水平降低［0.41 (0.27, 0.85) μg/L vs. 0.46 (0.35, 1.41) μg/L,P<0.05］,血浆UII水平与直立10 min后心率的变化次数呈负相关（相关系数-0.363, P<0.05）,血浆Cs浓度两组差异无统计学意义［0.48 (0.20, 1.91) μg/L vs. 0.52 (0.18, 1.60) μg/L,P>0.05］。结论：POTS患儿血浆UII水平降低,提示血管张力调节异常可能是POTS的发病机制之一。     

The role of human urotensin-II in patients with hypertrophic cardiomyopathy

Objective: Hypertrophic cardiomyopathy (HCM) is a genetic condition with the hallmark feature of left ventricular hypertrophy. Human Urotensin-II (hUT-II) is regarded as a cardiovascular autacoid/hormone, and it has cardiac inotropic and hypertrophic properties. Aims of this study were to elucidate the clinical significance of serum hUT-II levels as a potential new biomarker in patients with HCM.

Methods: This study included 40 HCM patients (60% males and 40% females) and were compared to 30 healthy control subjects (47% males and 53% females. All patients underwent extensive clinical, laboratory, and echocardiographic. Blood samples were taken to test for serum hUT-II levels by commercial ELISA Kit.

Results: Serum hUT-II was significantly higher (p < 0.01) in patients with HCM (15.8 ± 2.1 pmol/L) compared with healthy controls (3.3 ± 1.7 pmol/L). With regard to HCM patient, Serum hUT-II levels were significantly higher in the female with 16.3 ± 1.9 pmol/L than the male with 15.4 ± 2.2 pmol/L (p < 0.05). Among echocardiographic parameters, hUT-II was negatively associated with ejection fraction (r = -0.160, p = 0.324).

Conclusion: Results of the first study indicated that serum hUT-II levels were markedly elevated in patients with HCM. Serum hUT-II is a novel biomarker parameter that has clinical use in patients with the severity of LVH.     

血浆尾加压素Ⅱ水平与CCL4大鼠肝纤维化程度的关系

目的 研究血浆尾加压素Ⅱ(UⅡ)水平与肝纤维化病变程度的关系.方法 Wistar大鼠腹腔注射CCL4制备肝纤维化模型.肝纤维化组动物分别在4、6、8周处死.取肝组织测羟脯氨酸含量并观察肝脏病理学改变,采用ELISA方法分析检测UⅡ水平.结果 随模型制备时间延长血浆UⅡ水平逐渐升高,并与肝脏纤维化程度呈正相关.结论 UⅡ可能是参与肝纤维化发生、发展的重要因素.     

子痫前期孕妇血清与胎盘尿紧张素Ⅱ的表达及意义

目的:检测子痫前期孕妇外周血和新生儿脐血血清中尿紧张素Ⅱ(urotensinⅡ,UⅡ)水平和UⅡmRNA在胎盘组织的表达水平,探讨其在子痫前期发生发展中的作用。方法:(1)ELISA测定30例子痫前期患者及15例正常晚期妊娠孕妇(对照组)外周血和新生儿脐血血清UⅡ水平;(2)用RT-PCR法检测各组孕妇胎盘组织中UⅡmRNA的表达水平。结果:(1)重度子痫前期组孕妇外周血血清UⅡ水平明显高于轻度子痫前期组和对照组,差异均有显著性(P<0.05)。轻度和重度子痫前期组的脐静脉血清UⅡ浓度均明显高于对照组(P<0.05,P<0.001)。(2)胎盘组织UⅡmRNA表达水平在轻度和重度子痫前期组均明显高于对照组,差异有显著性(P<0.05)。结论:UⅡ可能参与子痫前期全身小血管痉挛的机制并在胎盘组织缺血缺氧和动脉粥样硬化的发生起重要作用。     

Endothelial nitric oxide synthase (eNOS) (Glu298Asp) and urotensin II (UTS2 S89N) gene polymorphisms in preeclampsia: prediction and correlation with severity in Egyptian females

Background: Preeclampsia is a leading cause of maternal and fetal/neonatal morbidity and mortality. Early prediction of preeclampsia can minimize maternal and fetal complications. Gene polymorphisms are promising markers for early prediction of preeclampsia. Aim of work: To assess the value of endothelial nitric oxide synthase (eNOS) (Glu298Asp) and urotensin II (UTS2 S89N) gene polymorphisms for early prediction of preeclampsia. Methods: The preeclamptic group consisted of 53 pregnant who developed preeclampsia (35 mild and 18 severe), while the control group consisted of 65 age-matched pregnant females who completed uncomplicated pregnancies. eNOS and urotensin II gene polymorphisms were tested using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Results: Concerning the eNOS gene polymorphism, there were highly significant differences between the two groups regarding the GG genotype as well as the G and T allele frequency (p?<?0.001) and a statistically significant differences regarding the GT, TT genotypes (p?=?0.002, 0.0276, respectively). Concerning the urotensin II gene polymorphisms, there were highly significant differences regarding the SS, SN genotypes as well as the S and N allele frequency (p?<?0.001), statistically significant differences regarding the NN genotype (p?=?0.063). Conclusion: Women having mutation in any of the two studied genes are at risk to develop mild preeclampsia, and those having mutations in both genes are at risk to develop severe preeclampsia, while the females with normal pregnancy are protected by the higher percentage of expression of the normal (wild allelles) of both genes.     

妊娠期高血压疾病患者血清尾加压素Ⅱ对心脏形态及功能影响的研究

目的探讨妊娠期高血压疾病患者血清尾加压素Ⅱ（UrotensinⅡ，UⅡ）水平对心脏形态及功能变化的影响。方法采用美国HP-5500型彩色多普勒超声诊断仪测量96例妊娠期高血压疾病患者及20例正常妊娠者孕晚期心脏房室腔大小、左室壁厚度，记录左室射血分数（EF）、心输出量（CO）、心脏指数（CI）作为评价心功能的指标，同时采用放射免疫法检测外周血中血清UⅡ水平。结果（1）与正常妊娠组对比，妊娠期高血压疾病组左室舒张末期室间隔厚度（IVSTd）、左室后壁厚度（LVPWTd）、左房收缩末期内径（LAD）均增加（P〈0．01或〈0．05），血清UⅡ水平升高，且其水平与上述各项指标均呈显著正相关关系（P均〈0．05）。（2）左室功能比较，妊娠期高血压疾病各组CO、CI、EF与正常妊娠组相比，差异无显著性意义（P均〉0．05）。结论妊娠期高血压疾病患者妊娠晚期血清UⅡ水平与心脏形态及功能改变有关，UⅡ可能参与妊娠期高血压疾病的心脏变化过程。